Xenopus δ-catenin is essential in early embryogenesis and is functionally linked to cadherins and small GTPases

Abstract

Catenins of the p120 subclass display an array of intracellular localizations and functions. Although the genetic knockout of mouse δ-catenin results in mild cognitive dysfunction, we found severe effects of its depletion in Xenopus. δ-catenin in Xenopus is transcribed as a full-length mRNA, or as three (or more) alternatively spliced isoforms designated A, B and C. Further structural and functional complexity is suggested by three predicted and alternative translation initiation sites. Transcript analysis suggests that each splice isoform is expressed during embryogenesis, with the B and C transcript levels varying according to developmental stage. Unlike the primarily neural expression of δ-catenin reported in mammals, δ-catenin is detectable in most adult Xenopus tissues, although it is enriched in neural structures. δ-catenin associates with classical cadherins, with crude embryo fractionations further revealing non-plasma-membrane pools that might be involved in cytoplasmic and/or nuclear functions. Depletion of δ-catenin caused gastrulation defects, phenotypes that were further enhanced by co-depletion of the related p120-catenin. Depletion was significantly rescued by titrated p120-catenin expression, suggesting that these catenins have shared roles. Biochemical assays indicated that δ-catenin depletion results in reduced cadherin levels and cell adhesion, as well as perturbation of RhoA and Rac1. Titrated doses of C-cadherin, dominant-negative RhoA or constitutively active Rac1 significantly rescued δ-catenin depletion. Collectively, our experiments indicate that δ-catenin has an essential role in amphibian development, and has functional links to cadherins and Rho-family GTPases.